Donepezil and Memantine

NAMZARIC is indicated for the treatment of moderate to severe dementia of the Alzheimer’s type in patients stabilized on 10 mg of donepezil hydrochloride once daily. NAMZARIC is a combination of memantine hydrochloride, an NMDA receptor antagonist, and donepezil hydrochloride, an acetylcholinesterase inhibitor, indicated for the treatment of moderate to severe dementia of the Alzheimer’s type in patients stabilized on 10 mg of donepezil hydrochloride once daily.

NAMZARIC capsules contain two approved medications: memantine hydrochloride and donepezil hydrochloride. Each of those medications is postulated to have a different mechanism in Alzheimer’s disease. Memantine Persistent activation of central nervous system NMDA receptors by the excitatory amino acid glutamate has been hypothesized to contribute to the symptomatology of Alzheimer’s disease. Memantine is postulated to exert its therapeutic effect through its action as a low to moderate affinity uncompetitive (open channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels. There is no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer’s disease.

For patients on donepezil hydrochloride 10 mg only, the recommended starting dose of NAMZARIC is 7 mg/10 mg, taken once daily in the evening. The dose should be increased in 7 mg increments to the recommended maintenance dose of 28 mg/10 mg. The minimum recommended interval between dose increases is one week. Patients on memantine hydrochloride (10 mg twice daily or 28 mg extended-release once daily) and donepezil hydrochloride 10 mg once daily can be switched to NAMZARIC 28 mg/10 mg, taken once daily in the evening. NAMZARIC can be taken with or without food, whole or sprinkled on applesauce, do not divide, chew, or crush. Severe renal impairment: the recommended maintenance dose for NAMZARIC is 14 mg/10 mg once daily in the evening.

NAMZARIC is contraindicated in patients with known hypersensitivity to memantine hydrochloride, donepezil hydrochloride, piperidine derivatives, or to any excipients used in the formulation.

NAMZARIC is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia. NAMZARIC may have vagotonic effects on the sinoatrial and atrioventricular nodes manifesting as bradycardia or heart block. Monitor patients for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers. NAMZARIC can cause diarrhea, nausea, and vomiting. NAMZARIC may cause bladder outflow obstructions. Conditions that raise urine pH may decrease the urinary elimination of memantine, resulting in increased plasma levels of memantine.

The following serious adverse reactions are discussed below and elsewhere in the labeling. Cardiovascular Conditions Peptic Ulcer Disease and Gastrointestinal Bleeding Nausea and Vomiting Genitourinary Conditions Seizures Pulmonary Conditions The most common adverse reactions, occurring at a frequency of at least 5% and greater than placebo with memantine hydrochloride extended-release 28 mg/day, were headache, diarrhea, and dizziness. The most common adverse reactions, occurring at a frequency of at least 5% in patients receiving donepezil hydrochloride and at twice or more the placebo rate, include diarrhea, anorexia, vomiting, nausea, and ecchymosis.

Combined use with NMDA antagonists: use with caution. NAMZARIC may interfere with anticholinergic medications. Concomitant administration of succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists may lead to synergistic effect.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).